1. Sexy X Wimpy Y Jenny Graves La Trobe, UCanberra, ANU Beginnings of our XY Sex chromosomes are weird The disappearing Y Weird animal genomes, sex and the future of men the future of men Human XY and sex

2. JennyTech Labs, La Trobe 2001

3. testicles

4. Human sex and sex chromosomes female male X X X Y TDF testis hormones

5. Where is TDF? Female Male XXXY

6. TDF IS ON THE Y CHROMOSOME

7. Zooming in on TDF

9. SRY is the right gene SOX3 ancestor of SRY Discovery of the testis determining gene ZFY is the wrong gene! Jamie Foster, Andrew Sinclair SOX9 target of SRY

10. X and Y chromosomes are weird X 1669 genes Many different functions Many sex, intelligence genes Brains-and-balls genes Y Only 27 genes specific to Y Many copies, pseudogenes Male-specific functions Sex and spermatogenesis PAR Shared by X and Y Contains 24 genes Smart, Sexy X Wimpy Y

11. Problems at meiosis Dosage problems Sex-linked diseases Sex-reversal syndromes Why so weird? so they work optimally? evolutionary accident? XXXXXXXXXXXXXXXXX X Y Dumb design! Sex chromosomes are trouble

12. X Y proto-XY XY evolution Once the X and Y were an autosome pair One partner acquires a male-determining gene Nearby genes acquire male-advantage functions - recombination suppressed Y degraded by deletion, mutation And degraded and degraded The Y is a degraded X

13. MAMMALS Fish 450 TETRAPODS Amphibians 410 Monotremes 166 AMNIOTES Birds and Reptiles 310 Placental mammals Marsupials 148 Beginnings of our XY Human mice million years 105

14. Mammals Amniotes Tetrapods Fish Amphibians Reptiles and birdsMonotremes Marsupials Placentals 450 410 310 166 148 XY Origin of human sex chromosomes Human Mouse 105 X Elephant Map human X genes/DNA in other species

15. Sex chromosomes in weird animals kangaroos are XX female, XY male 1 2 3 4 5 6 7 X Y

16. Map kangaroo homologues of human X genes e.g. XPCT PGK X X Is it the same XY? Paint kangaroo X DNA onto human chromosomes Human Xq = kangaroo X.. ZFX.. 5 5 Human Xp = kangaroo 5 Mostly

17. Y X Origin of human XY Elephant X XA Kangaroo Human Map orthologues of human X genes

18. Y Chicken Platypus Kangaroo ElephantHuman X 6 41qA XAX Origin of human XY

19. Platypus sex chromosomes

20. Platypus sex chromosomes? Female: 26 pairs

21. Platypus sex chromosomes? X 1 Y 1 X 2 Y 2 X 3 Y 3 X 4 Y 4 X 5 Y 5 ? ? ? ? ? ?? ? ? ? Female: 26 pairsMale: 21 pairs + 10

22. The New York Times, December 2004

23. X1X1 X2X2 X3X3 X4X4 X5X5 Y5Y5 Y4Y4 Y3Y3 Y2Y2 Y1Y1 Platypus sex chromosomes at meiosis 5X + 5Y Telomere sequences mark chromosome ends Grutzner et al, Nature 2004

24. Genes on platypus sex chromosomes No homology to human X Platypus genome project Veyrunes, Waters Gen. Res. 2008 Homology to chicken Z DMRT1

25. Y Chicken Platypus Kangaroo ElephantHuman X 6 41qA XAX Origin of human XY

26. Male Female Z Z Z W Bird sex W is a degraded Z Chicken Emu No SRY Sex gene is DMRT1

27. Temperature Sex Determination - TSD e.g. Crocodiles and marine turtles Bird ZW = a turtle autosome Chick Z paint 6 6 Epigenetic sex

28. MAMMALS AMNIOTES TETRAPODS Fish Amphibians Reptiles and birdsMonotremes Marsupials Placentals 450 410 310 166 148 XY A Age of human sex chromosomes MYMY SRY SRY is 148-166 million years old A A SOX3 SRY

29. 166 million years ago – the Y had 1669 genes Today – the Y has 45 genes Genes lost per MY = ~1624/166 = ~9.8 At this rate Y will disappear in 4.6 MY END OF THE Y WHEN?

30. Will males disappear? New sex determining genes? Parthenogenic females? XXXXXXXXXXXXXXXX

31. Hope for men ! Amami-Osima Island Tokunoshima Island Okinawa-jima Island Tokunoshima spiny rat (T. tokunoshimensis) Amami spiny rat (T. osimensis) Okinawa spiny rat (T. muenninki ) female male XO XO no SRY Koroiwa et al, 2010 SRY female male XX XY no SRY female male XO XO Japanese spiny rats have survived loss of Y

32. What if XX spiny rat woman man War of the sex genes Infertility –> species divergence New hominid species?

33. Team Platypus : Frank Grutzner, Pat Miethke, Paul Waters, Daniel Macmillan Janine Deakin, Ke Jun Wei Snakes Denis O’Meally Yoichi Matsuda Team Dragon Arthur Georges, Alex Qinn,Tariq Ezaz, Janine Deakin, Kazumi Matsubara, Claire Hollely Frogs Ikuo Miura Nis El-Moghabel Emu Swathi Shetty ARC ARC ARC ARC

34. Genes on the human sex chromosomes p22 p21 p11 q11 q12 q13 q21 q22 q23 q24 q25 q26 Q27 q28 SNF addiction to sentimental movies NAG repetitive requests to tidy up BTT I8U mate choice locus U2 TTTT playful but irritating mating behaviour ICU X-ray vision to detect clandestine mating behaviour YAX tendency to long phone conversations MT inability to fill gas tank of car ITS9 inability to set electronic alarm clock EH? response to smutty jokes BOT husband’s credit card control locus RT pretensions to cultural activities MAC8 susceptibility to eating disorders PMT cyclical mood variation BCH-E ZZZ response to exciting televised cricket necessity to reorient directions when driving south PNP SNS Jane Austen appreciation locus MR MAP X Y

35. Don’t laugh at weird animals THE FAR SIDE Garry Larsen MORAL

36. Graves lab Sex and Y team Andrew Sinclair Jamie Foster Francine Brennan Patrick Western Rob Glas Swathi Shetty Andrew Pask Roland Toder Rachael O’Neill Margaret Delbridge Paul Waters Janine Deakin Frank Grützner Fred Veyrunes Mary Wallis Tariq Ezaz Veronica Murtagh Denis O’Meally Claudia Rodriguez Delgano Collaborators Marilyn Renfree Univ. Melbourne Fujiyama, Matsuda, Miura NIG, Nagoya, Hiroshima Malcolm Ferguson-Smith Cambridge Arthur Georges, Steve Sarre Univ. Canberra Friendly Genome Centres Wash U`Wes Warren JGIJeff Boore, Gerry Rubin SangerMark Ross UConnRachel O’Neill, Andy Pask